Intake of drugs by the inhalation route has an important role to obtain rapid effects in the treatment of respiratory diseases such as asthma and COPD because the drugs delivered by the inhalation route instantly start their activity there when administered directly to the respiratory tract. Compared with the oral and the parenteral route, administration of the drug by the oral route provides the desired effect in a shorter time and at lower doses of the drugs. In addition, possibility of occurrence of side effects is decreased and/or severity of the side effects is alleviated owing to administration of the drug directly to the target area and its use at lower doses. As the active agents taken by the inhalation route in the treatment of respiratory tract diseases are very potent, use of very low doses of these drugs is sufficient in order to obtain the required effect. The active agent is diluted with various excipients in course of production so as to eliminate the problems that would be encountered in production and use as a result of use of the active agent at very low doses. Furthermore, the excipients in the formulation enable to carry the active agents to the respiratory tract of the patient since they adsorb the active agents to their surfaces. Since amount of excipient used in the production of the formulation is quite higher than the amount of active agent, characteristics of the formulation are influenced by the selection and features of the excipient chosen.
Dry powder formulations are generally inhaled from blisters and capsule packs. The most significant factor which negatively affects the pharmaceutical quality of the dry powder formulations developed in order to be inhaled from capsules is moisture. Due to the material they are made of, capsules absorb moisture and the moisture diffuses into the capsule. The medicament exposed to moisture in the capsule is disintegrated in a short time; adheres to the inner surface of the capsule and the medicament is agglomerated. This results in administration of a lower amount of the active agent than the required amount for an effective treatment during the inhalation. Moreover, the capsules exposed to moisture are deformed in time. Therefore, problems occur while the capsules are pierced and/or the capsules cannot be pierced completely. In order to eliminate all these problems; many formulations, new production methods for these formulations and capsules have been developed in the prior art. These methods and capsules developed are generally high priced. In the patent application numbered US20060115432 (A1), a process applied to improve the features of lactose used in the formulation is disclosed. However, no solution is suggested so as to eliminate the problems resulting from the capsule moisture mentioned above. In the patent numbered EP1379220 (B1), a capsule made of a material with reduced moisture content which contains dry powder formulations comprising tiotropium as mixed with a physiologically acceptable excipient is disclosed. However, production of the capsule of materials with reduced moisture content does not bring long term solutions to problems resulting from moisture content of the capsule material. The capsule disclosed in this patent remains incapable in entirely eliminating the possibility of moisture absorption of the capsule due to the humidity of air and the conditions in course of production.
The inventors have developed a process enabling to eliminate or minimize the abovementioned problems for production of formulations comprising active agents effective in the treatment of respiratory tract diseases such as asthma and COPD.